Protein misfolding disorders (PMDs) include Alzheimer's disease, Parkinson's disease, type 2 diabetes, Huntington's disease, amyotrophic lateral sclerosis, systemic amyloidosis, prion diseases, and the like. Misfolded aggregates of different proteins may be formed and accumulate. The misfolded aggregates may induce cellular dysfunction and tissue damage, among other effects.
For example, Alzheimer's disease (AD) is a degenerative brain disorder with no effective treatment or accurate preclinical diagnosis. Evidence to date suggests that the misfolding, aggregation, and brain deposition of the amyloid-beta protein (Aβ) may be triggering factors for AD pathology. While Aβ plaques were originally thought to be the hallmark of the disease, current research suggests that soluble Aβ oligomers may be critical synapto-toxic species causing neurodegeneration in AD. Because the brain has low regeneration capacity, early diagnosis of AD is crucial to permit intervention before irreversible neuropathological changes occur. Several lines of evidence indicate that the process of Aβ misfolding and oligomerization may begin years or decades before the onset of clinical symptoms and substantial brain damage. Current diagnosis of AD may include clinical examination complemented by imaging techniques used mainly to rule out other forms of dementia. Definitive diagnosis is done post-mortem by histological examination of the brain for the presence of amyloid plaques and neurofibrillary tangles. Still, the lack of a widely accepted early, sensitive, and objective laboratory diagnosis remains a major problem for AD care.
The present application appreciates that diagnosis of AD may be a challenging endeavor.